1. Technical Field
The present invention relates to a composition for maturing dendritic cells, and a method for preparing antigen-specific dendritic cells using the same.
2. Description of the Related Art
Dendritic cells (DCs) are antigen-presenting cells (APCs) that have the most potent ability to present antigens among cells of the immune system. A dendritic cell stimulates a T cell that has not been exposed to antigen (termed naïve T cell), inducing an immune reaction. Hence, a dendritic cell is a unique immune cell that, unlike other APCs, can both effectively induce a primary immune response and activate memory T cells. A dendritic cell is known to express co-stimulatory molecules at a high concentration as well as MHC molecules (I/II) on the surface thereof, and to release cytokines (IFN-alpha, IL-12, IL-18) necessary for T cell activation. This is why dendritic cells can induce a potent immune response. Releasing Th1 immunity related cytokines such as IFN-alpha, IL-12, etc., type 1 dendritic cells can induce the proliferation of antigen-specific Th1 cells and the activation of cytotoxic T lymphocytes (CTL), and thus have useful applications in immunotherapy.
For utilizing dendritic cells in the immunotherapy of cancer, a technique for in vitro differentiating monocytes into dendritic cells and maturating the immature dendritic cells to mature ones useful in inducing T cell immunity is indispensable. Neither techniques of preparing immature dendritic cells from monocytes in vivo nor a maturation process have yet been standardized in the art. Particularly, the maturation of the immature dendritic cells differentiated from monocytes is achieved through a process in which the immature dendritic cells are allowed to migrate to lymph nodes where they present an antigen fragment to näive T cells to induce a Th1 immune response. Fully mature dendritic cells express MHC I and II molecules and T cell co-stimulatory molecules, i.e., CD80 and CD86, at a high concentration on their surface, compared to immature dendritic cells. In addition, mature dendritic cells secrete many of cytokines that are directly involved in the induction of T cell immune responses. After undergoing this change by maturation, the dendritic cells greatly increase in the potential of inducing T cell immune responses.
MCM (monocyte conditioned medium) is known as being useful for the maturation of dendritic cells. MCM, which produced by culturing monocytes in vitro, is used as a source of maturation factors. MCM approach, however, does not guarantee an uniform condition from one maturation process to another because proinflammatory cytokines that monocytes release in response to external signals greatly vary in quantity from person to person. In addition, an additional disadvantage is the requirement of a large quantity of peripheral blood monocytes for preparing MCM. As an alternative to the MCM approach, a cytokine cocktail of important cytokines (IL-1β, IL-6, TNF-α, PGE2) selected from among MCM components was developed. The cytokine cocktail can allow for the stable production of dendritic cells with relatively high function, as well as solving the problems of MCM. However, the cytokine cocktail alone cannot render sufficiently mature dendritic cells.
Korean Patent Application Unexamined Publication No. 10-2011-0035633 discloses the in vitro generation of cytotoxic T cells by using Th1 cells and dendritic cells. However, since this method utilizes dendritic cells that are not yet matured fully, it is difficult to expect substantially sufficient immunotherapy therefrom.
There is therefore a strong need for a more effective maturation technique of dendritic cells by which potent antigen-specific immunity against cancer can be induced, leading to a maximum immunotherapeutic effect on cancer.